Abstract

OBJECTIVE—Nocturnal hypoglycemia represents an important problem for diabetic patients, which has been primarily attributed to an attenuated
hormonal counterregulation during sleep. So far, hypoglycemia counterregulation has been exclusively examined during early
nocturnal sleep, although early sleep differs markedly in sleep stage architecture from late sleep. Here, we investigated
whether awakening and counterregulatory responses differ between early and late sleep.

RESEARCH DESIGN AND METHODS—Sixteen healthy subjects were tested on three occasions. On two nights, a linear fall in plasma glucose to a nadir of 2.2
mmol/l within 60 min was induced by insulin infusion. On one night, this was done immediately after sleep onset and on the
other night after ∼3.5 h of sleep. In a further control night, no hypoglycemia was induced.

RESULTS—During early sleep, 10 subjects awoke in response to hypoglycemia, whereas no subject awoke during the corresponding interval
of the control night (P < 0.004). During late sleep, all subjects awoke upon hypoglycemia, and four subjects awoke spontaneously during the corresponding
control interval (P < 0.001). The pattern indicates that the frequency of awakenings caused by hypoglycemia is similar for early and late sleep.
Increases in epinephrine, norepinephrine, ACTH, cortisol, and growth hormone were distinctly weaker during late than early
hypoglycemia (all P < 0.05).

CONCLUSIONS—Diminished hormonal counterregulation during late sleep could be one factor contributing to the clinically observed accumulation
of hypoglycemic episodes in the later part of the night in patients with diabetes.

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